Dopa-responsive dystonia: some pieces of the puzzle are still missing.

The profound and sustained benefit of levodopa to a child with dopa-responsive dystonia (DRD) provides a compelling reason to be aware of DRD; however, neurologists probably under-recognize this disorder. Four articles examining the pathophysiologic basis of DRD and its potential ramifications appear in this issue of Neurology . Dystonia is a syndrome of sustained muscle contractions, frequently causing twisting or repetitive movements, and can lead to sustained postures.1 Whereas the cause of dystonia in most affected individuals remains elusive, a genetic etiology is identified in a larger proportion of patients in whom the disorder was previously classified as"idiopathic." The distinction of DRD from the background of idiopathic dystonia occurred with the dawn of the levodopa era for Parkinson's disease, almost 30 years ago. Most early reports of DRD were anecdotal and presented cases under a variety of designations. Whereas Dr. Masaya Segawa of Tokyo, Japan was not the first to report such a case, he was the first to delineate many of the particular characteristics of this disorder in a series of patients affected with "hereditary progressive dystonia with marked diurnal fluctuation."2 These patients were generally considered unique to Japan and it was not until some 15 years later that this syndrome was considered to have worldwide distribution.3 The important clinical features of DRD are onset of dystonia, usually affecting gait, in childhood; the concurrent or subsequent development of parkinsonian signs; and a dramatic therapeutic response to levodopa.3 A frequent, but not invariable, observation is the worsening of signs and symptoms in a patient later in the day (diurnal fluctuation). Approximately half of index cases with DRD report a family member affected with a similar disorder. The closer scrutiny given to these patients and their families extended the clinical phenotype in DRD. Hyperactive stretch reflexes and …